{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T16:59:23Z","timestamp":1775235563844,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17824969"],"award-info":[{"award-number":["17824969"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17KT0051"],"award-info":[{"award-number":["17KT0051"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H04971"],"award-info":[{"award-number":["18H04971"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H03407"],"award-info":[{"award-number":["20H03407"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Scoliosis, usually diagnosed in childhood and early adolescence, is an abnormal lateral curvature of the spine. L\u2010type amino acid transporter 1 (LAT1), encoded by solute carrier transporter 7a5 (<jats:italic>Slc7a5<\/jats:italic>), plays a crucial role in amino acid sensing and signaling in specific cell types. We previously demonstrated the pivotal role of LAT1 on bone homeostasis in mice, and the expression of LAT1\/<jats:italic>SLC7A5<\/jats:italic> in vertebral cartilage of pediatric scoliosis patients; however, its role in chondrocytes on spinal homeostasis and implications regarding the underlying mechanisms during the onset and progression of scoliosis, remain unknown. Here, we identified LAT1 in mouse chondrocytes as an important regulator of postnatal spinal homeostasis. Conditional inactivation of LAT1 in chondrocytes resulted in a postnatal\u2010onset severe thoracic scoliosis at the early adolescent stage with normal embryonic spinal development. Histological analyses revealed that <jats:italic>Slc7a5<\/jats:italic> deletion in chondrocytes led to general disorganization of chondrocytes in the vertebral growth plate, along with an increase in apoptosis and a decrease in cell proliferation. Furthermore, loss of <jats:italic>Slc7a5<\/jats:italic> in chondrocytes activated the general amino acid control (GAAC) pathway\u00a0but inactivated the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the vertebrae. The spinal deformity in <jats:italic>Slc7a5<\/jats:italic>\u2010deficient mice was corrected by genetic inactivation of the GAAC pathway, but not by genetic activation of the mTORC1 pathway. These findings suggest that the LAT1\u2010GAAC pathway in chondrocytes plays a critical role in the maintenance of proper spinal homeostasis by modulating cell proliferation and survivability.<\/jats:p>","DOI":"10.1002\/jcp.30883","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T19:26:16Z","timestamp":1664220376000},"page":"4292-4302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Conditional inactivation of the L\u2010type amino acid transporter LAT1 in chondrocytes models idiopathic scoliosis in mice"],"prefix":"10.1002","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3346-1981","authenticated-orcid":false,"given":"Sayuki","family":"Iwahashi","sequence":"first","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajun","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Tokumura","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoma","family":"Osumi","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manami","family":"Hiraiwa","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Kubo","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuhiro","family":"Horie","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Demura","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriaki","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Ichinomiya Nishi Hospital  Ichinomiya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Saito","sequence":"additional","affiliation":[{"name":"Sensory and Motor System Medicine, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyujin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Fukasawa","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Iezaki","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akane","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akane","family":"Tomizawa","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Ochi","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation for Motor Functions, Research Institute National Rehabilitation Center for Persons with Disabilities  Tokorozawa, Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Hojo","sequence":"additional","affiliation":[{"name":"Center for Disease Biology and Integrative Medicine, Graduate School of Medicine The University of Tokyo  Tokyo Japan"},{"name":"Department of Bioengineering, Graduate School of Engineering The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Ohba","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Institute of Biomedical Sciences Nagasaki University  Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiichi","family":"Hinoi","sequence":"additional","affiliation":[{"name":"Department of Bioactive Molecules, Pharmacology Gifu Pharmaceutical University  Gifu Japan"},{"name":"United Graduate School of Drug Discovery and Medical Information Sciences Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1748-7161-1-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300761200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22275.1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivs045"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/bcj20160822"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874325001610010143"},{"key":"e_1_2_7_8_1","first-page":"261","article-title":"Outline for the study of scoliosis","volume":"5","author":"Cobb J.","year":"1948","journal-title":"American Academy of Orthopaedic Surgeons Instructional Course Lectures"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.22603\/ssrr.2021-0189"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620x.85b7.14046"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20236009"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1212704"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21456"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.164004"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12869"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.05.008"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181891751"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v99.3.736"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2018.02.006"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaw3921"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089547"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2556"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200302066"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1748-7161-7-7"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.043281"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.069575"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11151"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0005-2736(01)00384-4"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.564809"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28166"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004820"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30883","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.30883","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30883","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T06:57:50Z","timestamp":1692601070000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.30883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,26]]},"references-count":30,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/jcp.30883"],"URL":"https:\/\/doi.org\/10.1002\/jcp.30883","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,26]]},"assertion":[{"value":"2022-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}